Retrospective web-based multicenter evaluation of ¹8F-FDG-PET and CT derived predictive factors. Radioimmunotherapy with yttrium-90-ibritumomab tiuxetan in follicular non Hodgkin's lymphoma.

AIM: Although predictive factors (PF) for conventional lymphoma therapy are established and frequently used in clinical practice and medical research, the PF for radioimmunotherapy (RIT) have not been fully defined until now. The aim of this multicenter evaluation is to prove the feasibility of the multicenter web-based data collection and to preliminary explore imaging findings and prediction of therapy response in patients with follicular lymphoma (FL) following radioimmunotherapy (RIT) with 90Y-ibritumomab tiuxetan. PATIENTS, METHODS: We retrospectively analyzed and correlated clinical and imaging data (CT and FDG-PET) before and after RIT as documented by the RIT-Network. Evaluation of treatment response was done on both patient and lesion basis. Every measurable lesion was analyzed in terms of standardized uptake value (SUV), volume (CT and PET) and response. PF were identified using a uni- and multivariate model. A web-based system was used for the documentation and evaluation of clinical and imaging data. RESULTS: 16 patients with at least one PET before and after RIT were eligible for analysis. Concerning response three months postRIT, 5 patients achieved a CR, 6 patients a PR and 4 patients remained with NC. A total of 159 lesions were measured (mean 10±8). In the multivariate model the log lesion volume (p < 0.0001), the total (p = 0.03) and maximum lesion volume (p = 0.05) were predictors for response (CR + PR). Concerning the lesional CR initial small lesion volume (p = 0.009) and its high metabolic activity (p = 0.01) were identified as predictors. The web-based system showed no major disturbances allowing secure data transfer and central image interpretation in a reasonable time. CONCLUSION: The use of a web-based multicenter archiving system for clinical and imaging data is technically feasible in a multicenter setting and allows a central analysis. This preliminary analysis suggests that FDG-PET may predict the likelihood of response to RIT.

Physical aspects of scintigraphy-based dosimetry for nuclear medicine therapy.

In nuclear medicine therapy the treatment of tumours by radiation exposure from internally deposited labelled antibodies or labelled peptides is currently an active field of investigation. To permit the efficient delivery of high amounts of radiation dose to tumours while limiting the radiation dose to critical organs dosimetry calculations have to be performed. These are relying on scintigraphic data being input to the well known MIRD formalism. This paper focuses on the methods and the difficulties associated with the scintigraphic determination of organ kinetics. The physical properties of the well-known scintigraphic imaging modalities, PET, SPECT and planar scintigraphy, are discussed thereby taking into account the properties of the appropriate radionuclides currently being available for therapy and dosimetry. Several arguments are given and disputed for the limited clinical use of PET and SPECT in dosimetry and the ongoing preference of planar whole-body imaging as the method of choice. The quantitative restrictions still inherent to this method are also discussed in detail. Procedural recommendations are proposed covering all processes related to data acquisition, data correction and data analysis which finally lead to reliable estimations of organ dose.

Radiosynoviorthesis of medium-sized joints with rhenium-186-sulphide colloid: a review of the literature.

Hypertrophy and inflammation of the synovium with various underlying pathologies - such as rheumatoid arthritis, osteoarthritis, haemophilia and spondyloarthropathy - can be treated successfully by radiosynoviorthesis (RSO). For medium-sized joints (shoulder, elbow, wrist, hip and ankle), the radionuclide of choice is rhenium-186. We review the evidence for the efficacy of this local, relatively non-invasive therapy and evaluate its benefits and risks. We conclude good evidence of rhenium-186 RSO in rheumatoid arthritis and haemophilic arthropathy. In the remaining pathologies, up to now, the therapeutic efficacy has not been confirmed by today's most stringent criteria for clinical studies. The available data support rhenium-186 RSO as a suitable second-line treatment for patients in whom other therapies (including locally injected corticoids) have failed, as long as proper attention is paid to correct administration - including post-treatment immobilization and the co-administration of corticoids.

Therapeutic status of radiosynoviorthesis of the knee with yttrium [90Y] colloid in rheumatoid arthritis and related indications.

Radiosynoviorthesis (RSO) with an yttrium-90 colloid offers a local and minimally invasive therapy for treating inflammatory hypertrophy of the synovial membrane of the knee that has arisen from numerous kinds of disorder: these include rheumatoid arthritis (RA), osteoarthritis (OA), spondyloarthropathy, villonodular synovitis and others. There is substantial evidence that this treatment is efficacious and that, in view of the benefits that it offers, its tolerability and safety are very good. Administration should be restricted to patients in whom other therapies (including locally injected corticoids) have failed, and proper attention must be paid to correct administration, including post-treatment immobilization and the co-administration of corticoids, to minimize the risk of leakage and of efflux through the puncture channel.

The effect of the beta-emitting yttrium-90 citrate on the dose-response of dicentric chromosomes in human lymphocytes: a basis for biological dosimetry after radiosynoviorthesis.

The production of dicentric chromosomes in human lymphocytes by beta-particles of yttrium-90 (Y-90) was studied in vitro to provide a basis of biological dosimetry after radiosynoviorthesis (RSO) of persistent synovitis by intra-articular administration of yttrium-90 citrate colloid. Since the injected colloid may leak into the lymphatic drainage exposing other parts of the body to radiation, the measurement of biological damage induced by beta-particles of Y-90 is important for the assessment of radiation risk to the patients. A linear dose-response relationship (alpha = 0.0229 +/- 0.0028 dicentric chromosomes per cell per gray) was found over the dose range of 0.2176-2.176 Gy. The absorbed doses were calculated for exposure of blood samples to Y-90 activities from 40 to 400 kBq using both Monte Carlo simulation and an analytical model. The maximum low-dose RBE, the RBE(M) which is equivalent to the ratio of the alpha coefficients of the dose-response curves, is well in line with published results obtained earlier for irradiation of blood of the same donor with heavily filtered 220 kV X-rays (3.35 mm copper), but half of the RBE(M) relative to weakly filtered 220 kV X-rays. Therefore, it can be concluded that for estimating an absorbed dose during RSO by the technique of biological dosimetry, in vitro and in vivo data for the same radiation quality are necessary.

[Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan. Clinical considerations, radiopharmacy, radiation protection, perspectives]. / Radioimmuntherapie mit 90Y-markiertem Ibritumomab-Tiuxetan: Klinik, Radiopharmazie, Strahlenschutz, Perspektiven.

90Y-ibritumomab tiuxetan (Zevalin) is currently approved for radioimmunotherapy of patients with relapsed or refractory follicular non-Hodgkin's lymphoma pretreated with rituximab. Future directions are the combined use of 90Y-ibritumomab tiuxetan as part of the initial treatment and as first-line multi-agent therapy of relapsed disease. Current studies investigate patients with other than follicular indolent histologies, e. g. diffuse large cell lymphoma. Labelling of 90Y ibritumomab tiuxetan is a safe procedure, the radiochemical purity is not disturbed by a higher room temperature or by metallic impurity. Quality control is recommended by thin layer chromatography (TLC), strips >15 cm are favourable. TLC cannot distinguish between the correctly radiolabelled antibodies and radiocolloid impurity. If necessary, additional HPLC should be performed. Radiocolloid impurities are absorbed to the solid phase and do not reach the eluate. If the radiochemical purity test is insufficient (<95%), the additional cleaning using EconoPac 10 DG columns (Biorad, Hercules, CA, USA) is a reliable procedure to reduce the percentage of free radionuclide. However, this procedure is not part of the approval.

Persistent vegetative state: evaluation of brain metabolism and brain perfusion with PET and SPECT.

Patients in persistent vegetative state (PVS) after severe head trauma were investigated with 99mTc-ECD SPECT and 18F-FDG PET to further characterize the degree of brain damage and to obtain insight into changes of brain perfusion and glucose metabolism. 18F-FDG PET and 99mTc-ECD SPECT were performed in 16 patients in PVS. Quantitative PET data were compared with that obtained from seven normal controls. After spatial normalization into Talairach space, global grey matter values and regional data using predefined ROI sets were derived. For comparison of PET and SPECT, regional data were normalized to their individual mean grey matter values. Patients in PVS showed significantly lower values of cerebral glucose metabolism than did the controls. The mean reduction of grey matter values in cortical and subcortical structures was 58%, except in the vermis cerebelli, where only a reduction of 16% was found compared to the controls. Comparing the glucose metabolism and perfusion within the patient group, the pattern of both modalities was similar in the neocortex and internal ganglia. In the cerebellar hemispheres a relatively higher perfusion than glucose metabolism was found. The overall reduction of 58% of glucose metabolism in grey matter structures is in accordance with other PET studies investigating PVS patients with different disease histories. The relative preserved activity of vermis cerebelli seems to be an uncommon finding not described by other authors up to now.

Accuracy of the intra-operative radioguided localization of the sentinel lymph node (SLN) 24 hours after lymphoscintigraphy in patients with malignant melanoma.

AIM: For optimized logistics for the sentinel lymphadenectomy (SL) it might be helpful for the clinics involved if a longer time period between the lymphoscintigraphy (LS) and surgery is possible. Therefore, we investigated if a precise localization of the sentinel lymph node is possible 24 hours after LS. METHODS: 78 patients with primary malignant melanoma (MM; n = 44) or with MM pre-operated by excisional biopsy (n = 34) were investigated. In 40 cases the tumor was localized on the trunk and in 38 cases on the extremities. Mean MM thickness was 2.68 mm (range: 0.29 to 12 mm). In all patients a lymphoscintigraphy (LS) with an average of 85 MBq of Tc-99m nanocolloid was performed one day prior to surgery. Immediately after tracer application dynamic data acquisition was started at a LFOV gamma camera followed by a whole body scan. With a hand-held gamma detector (C-Trak) 2, 4, 6, 8, and 24 hours after tracer administration the SLN was identified and the counts registered. RESULTS: 94 SLNs were identified in 87 lymphatic basins from which 86 could be resected. Nine MM showed two draining channels. After 24 hours 15.5% (as an average) of the initial counts could be measured in the SLN. The uptake in the SLN in pre-operated versus patients with primary tumor was statistically not significant (p = 0.4). In 16 cases (20.5%) the SLN was tumor positive. Four of those patients developed distant metastases and two died within the first year. None of the patients with negative SLN developed distant metastases or died. CONCLUSION: The remaining activity in the SLN up to 24 hours after administration is sufficient for their intra operative localization. The method of lymphoscintigraphy and localization of the SLN by a hand-held gamma detector optimizes the intra operative identification of the SLN in patients with malignant melanoma.

[Symptomatic cyst of the pancreas and asymptomatic bilateral phaeochromocytoma]

Symptomatic cyst of the pancreas and asymptomatic bilateral phaeochromocytoma. HISTORY AND CLINICAL FINDINGS: A 39-year-old woman was admitted to our department of gastroenterology with recurrent epigastrical pain. Ten years previously the diagnosis of von Hippel-Lindau (VHL)-syndrome has been established. Two years before a germ line mutation in exon 3 of the VHL-tumour suppressor gene has been detected. The patient has a healthy son with a normal VHL-gene and four healthy siblings who had refused a genetic blood test. INVESTIGATIONS: At abdominal ultrasound at the head of the pancreas three 4 2 cm large cysts and in the region of the left adrenal gland a 2,9 2,7 cm large tumor were visible. MRI of the abdomen revealed in addition a 2,2 1,5 cm large tumour of the right adrenal gland. An asymptomatic biadrenal phaeochromocytoma was detected by elevated urine catecholamines and 123I-MIBG-scintigraphy. TREATMENT AND COURSE: The cysts of the pancreas were punctured under endosonographical control and analysis of the cyst fluid was not suspicious of a malignant cystic tumour. The patient had no further abdominal complaints. After oral treatment with the alpha-blocker phentolamine the biadrenal phaeochromocytoma was treated by retroperitoneal laparoscopic surgery in an organ-sparing fashion. Postoperatively ACTH-stimulating test revealed a normal cortisol response. CONCLUSION: Adrenocortical function can be preserved by la-paroscopic adrenal-sparing surgery in bilateral phaeochromocytoma.